HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease

Journal
Science
ISSN
0036-8075
1095-9203
Date Issued
2020
Author(s)
Sarah A. Cook
William A. Comrie
Morgan Similuk
Andrew J. Oler
Aiman J. Faruqi
Douglas B. Kuhns
Sheng Yang
Alexander Vargas-Hernández
Alexandre F. Carisey
Benjamin Fournier
D. Eric Anderson
Susan Price
Margery Smelkinson
Wadih Abou Chahla
Lisa R. Forbes
Emily M. Mace
Tram N. Cao
Zeynep H. Coban-Akdemir
Shalini N. Jhangiani
Donna M. Muzny
Richard A. Gibbs
James R. Lupski
Jordan S. Orange
Geoffrey D. E. Cuvelier
Moza Al Hassani
Nawal Al Kaabi
Zain Al Yafei
Soma Jyonouchi
Nikita Raje
Jason W. Caldwell
Yanping Huang
Janis K. Burkhardt
Sylvain Latour
Baoyu Chen
Gehad ElGhazali
V. Koneti Rao
Ivan K. Chinn
Michael J. Lenardo
Type
Resource Types::text::journal::journal article
Scopus ID
2-s2.0-85087815993
WoS ID
WOS:000548753100045
DOI
URL
Abstract
<jats:title>An inherited disorder makes WAVEs</jats:title>
<jats:p>
The WAVE regulatory complex (WRC) is a multiunit complex that regulates actin cytoskeleton formation. Although other actin-regulatory proteins modulate human immune responses, the precise role for the WRC has not yet been established. Cook
<jats:italic>et al.</jats:italic>
studied five patients from four unrelated families who harbor missense variants of the gene encoding the WRC component HEM1. These patients presented with recurrent infections and poor antibody responses, along with enhanced allergic and autoimmune disorders. HEM1 was found to be required for the regulation of cortical actin and granule release in T cells and also interacted with a key metabolic signaling complex contributing to the disease phenotype. By linking these interactions to immune function, this work suggests potential targets for future immunotherapies.
</jats:p>
<jats:p>
<jats:italic>Science</jats:italic>
, this issue p.
<jats:related-article xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="doi" issue="6500" page="202" related-article-type="in-this-issue" vol="369" xlink:href="10.1126/science.aay5663">202</jats:related-article>
</jats:p>
Cite this document
Cook, S. A., Comrie, W. A., Poli, M. C., Similuk, M., Oler, A. J., Faruqi, A. J., Kuhns, D. B., Yang, S., Vargas-Hernández, A., Carisey, A. F., Fournier, B., Anderson, D. E., Price, S., Smelkinson, M., Abou Chahla, W., Forbes, L. R., Mace, E. M., Cao, T. N., Coban-Akdemir, Z. H., … Lenardo, M. J. (2020). HEM1 deficiency disrupts mTORC2 and F-actin control in inherited immunodysregulatory disease. Science, 369(6500), 202-207. https://doi.org/10.1126/science.aay5663
Project(s)
Subjects
actins

; 

adp-ribosylation factor 1

; 

cd4-positive t-lymphocytes

; 

cell proliferation

; 

cytokines

; 

humans

; 

immunologic deficiency syndromes

; 

lymphoproliferative disorders

; 

mechanistic target of rapamycin complex 2

; 

membrane proteins

; 

pedigree

; 

phosphorylation

; 

wiskott-aldrich syndrome protein family

; 

adenosine diphosphate ribosylation factor 1

; 

f actin

; 

hematopoietic cell kinase

; 

mammalian target of rapamycin complex 2

; 

protein hem1

; 

protein kinase b

; 

unclassified drug

; 

actin

; 

adenosine diphosphate ribosylation factor 1

; 

arf1 protein, human

; 

cytokine

; 

mammalian target of rapamycin complex 2

; 

membrane protein

; 

nckap1l protein, human

; 

wasf1 protein, human

; 

wasf2 protein, human

; 

wasf3 protein, human

; 

wiskott aldrich syndrome protein

; 

cell component

; 

chemical reaction

; 

disease

; 

immune response

; 

immune system

; 

immunity

; 

mutation

; 

polymerization

; 

protein

; 

actin polymerization

; 

article

; 

atopy

; 

cell migration

; 

cytokine overproduction

; 

cytokine production

; 

cytokine release

; 

disease association

; 

gene

; 

gene mutation

; 

human

; 

immune dysregulation

; 

immune response

; 

immunocompetent cell

; 

lymphocyte proliferation

; 

nckap1l gene

; 

priority journal

; 

protein depletion

; 

protein phosphorylation

; 

signal transduction

; 

synapse

; 

t lymphocyte

; 

biosynthesis

; 

cd4+ t lymphocyte

; 

cell proliferation

; 

chemistry

; 

genetics

; 

immune deficiency

; 

immunology

; 

lymphoproliferative disease

; 

metabolism

; 

pedigree

; 

phosphorylation

; 

physiology